Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study
BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3225 (Published 29 August 2018)
Katerina Trajanoska, PhD student1 2, John A Morris, PhD student3 4, Ling Oei, assistant professor1 2, Hou-Feng Zheng, professor5 6, David M Evans, professor7 8, Douglas P Kiel, professor9 10, Claes Ohlsson, professor11, J Brent Richards, professor3 4, Fernando Rivadeneira, associate professor1 2 on behalf of the GEFOS/GENOMOS consortium and the 23andMe research team
F Rivadeneira f.rivadeneira at erasmusmc.nl, and J B Richards brent.richards at mcgill.ca
Poor vitamin D genes are associated with many health problems.
Osteoporosis does not appear to be one of the problems
Osteoporosis (poor bone strenth) is, however, related to
low Vitamin D and poor gut (which decreases Vit D),
low protein
low Magnesium
low Boron
low Silica
low Exercise
low Vitamin K
low Calcium (but too much is bad)
- Osteoporosis and low grip strength both associated with low vitamin D – Feb 2018
- Osteoporosis 4X more likely if poor gut (probably poor vitamin D absorption) – Aug 2017
- American College of Rheumatology Guidelines finally include Vitamin D – June 2017
- Osteoporosis of Indian men in their 60’s (perhaps low vitamin D, K, and Mg) – Nov 2016
- Better bones again associated with higher vitamin K intake – Nov 2015
- Healthy bones need: Calcium, Vitamin D, Magnesium, Silicon, Vitamin K, and Boron – 2012
- Adding just vitamin D again failed to add bone density (also need Magnesium, Vitamin K, etc) – RCT Aug 2018
- Vitamin D, K2, Magnesium, etc increase bone density when taking together– Jan 2012
- 20X increase in vitamin D sold and 36 percent decrease in osteoporosis business in Australia – Nov 2013
- Strong bones need both physical activity and vitamin D – Jan 2013
Pages in BOTH the categories Osteoporosis and Meta-analysis
- Osteoporosis synergistically treated by bisphosphonates and Vitamin D - meta-analysis Nov 2024
- Vitamin D during pregnancy increased child’s bone mineral density – meta-analysis April 2023
- Osteoporosis Risk varies with Vitamin D Receptor – three meta-analyses in 2020
- Osteoporosis 15 percent more likely if poor Vitamin D receptor – meta-analysis Dec 2018
- Fractures reduced with any amount of vitamin D and some Calcium - Cochraine April 2014
- Vitamin D Receptor genes bb and BB and Osteoporosis, esp. for blacks – meta-analysis Nov 2012
- Hip fractures reduced 30 percent with 800 IU of vitamin D – meta-analysis July 2012
- Vitamin D for elderly 800 to 2000 IU - Osteoporosis Canada - Sept 2010
- Hip fractures in India - editorial with recommendation - Sept 2010
- Cochrane review finds that Vitamin D and Calcium treat osteoporosis – Feb 2010
Overview Osteoporosis and vitamin D contains the following summary
- FACT: Bones need Calcium (this has been known for a very long time)
- FACT: Vitamin D improves Calcium bioavailability (3X ?)
- FACT: Should not take > 750 mg of Calcium if taking lots of vitamin D (Calcium becomes too bio-available)
- FACT: Adding vitamin D via Sun, UV, or supplements increased vitamin D in the blood
- FACT: Vitamin D supplements are very low cost
- FACT: Many trials, studies. reviews, and meta-analysis agree: adding vitamin D reduces osteoporosis
- FACT: Toxic level of vitamin D is about 4X higher than the amount needed to reduce osteoporosis
- FACT: Co-factors help build bones.
- FACT: Vitamin D Receptor can restrict Vitamin D from getting to many tissues, such as bones
- It appears that to TREAT Osteoporosis:
- Calcium OR vitamin D is ok
- Calcium + vitamin D is good
- Calcium + vitamin D + other co-factors is great
- Low-cost Vitamin D Receptor activators sometimes may be helpful
- CONCLUSION: To PREVENT many diseases, including Osteoporosis, as well as TREAT Osteoporosis
- Category Osteoporosis has
221 items - Category Bone Health has
314 items Note: Osteoporosis causes bones to become fragile and prone to fracture
Osteoarthritis is a disease where damage occurs to the joints at the end of the bones
Osteoporosis category includes the following221 items in category - see also Overview Osteoporosis and vitamin D - Overview Fractures and vitamin D
- Bone - Health
314 items - VitaminDWiki pages with BONE MINERAL DENSITY or BMD in title 29+ pages
- Search VitaminDWiki for OSTEOPENIA 1740 items as of July 2020
13 articles are in both Osteroporosis and Vitamin D Receptor categories 10 articles are in both Osteroporosis and Meta-analysis categories - 20X increase in vitamin D sold and 36 percent decrease in osteoporosis business in Australia – Nov 2013
Download the PDF from VitaminDWiki
Objectives To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk.
Design Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach.
Setting 25 cohorts from Europe, United States, east Asia, and Australia with genome wide genotyping and fracture data.
Participants A discovery set of 37 857 fracture cases and 227 116 controls; with replication in up to 147 200 fracture cases and 150 085 controls. Fracture cases were defined as individuals (>18 years old) who had fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports. Instrumental variable analyses were performed to estimate effects of 15 selected clinical risk factors for fracture in a two-sample mendelian randomisation framework, using the largest previously published GWAS meta-analysis of each risk factor.
Results Of 15 fracture associated loci identified, all were also associated with bone mineral density and mapped to genes clustering in pathways known to be critical to bone biology (eg, SOST, WNT16, and ESR1) or novel pathways (FAM210A, GRB10, and ETS2). Mendelian randomisation analyses showed a clear effect of bone mineral density on fracture risk. One standard deviation decrease in genetically determined bone mineral density of the femoral neck was associated with a 55% increase in fracture risk (odds ratio 1.55 (95% confidence interval 1.48 to 1.63; P=1.5×10−68). Hand grip strength was inversely associated with fracture risk, but this result was not significant after multiple testing correction. The remaining clinical risk factors (including vitamin D levels) showed no evidence for an effect on fracture.
Conclusions This large scale GWAS meta-analysis for fracture identified 15 genetic determinants of fracture, all of which also influenced bone mineral density. Among the clinical risk factors for fracture assessed, only bone mineral density showed a major causal effect on fracture. Genetic predisposition to lower levels of vitamin D and estimated calcium intake from dairy sources were not associated with fracture risk.
Fractures are not a function of vitamin D genes – Aug 2018Printer Friendly Follow this page for updates5746 visitors, last modified 04 Sep, 2018, This page is in the following categories (# of items in each category)
- Category Bone Health has